title: Sustained production of ROS triggers compensatory proliferation and is required for regeneration to proceed.
abstract: A major issue in regenerative medicine is the role of injury in promoting cell plasticity. Here we explore the function of reactive oxygen species (ROS) induced through lesions in adult zebrafish. We show that ROS production, following adult fin amputation, is tightly regulated in time and space for at least 24 hours, whereas ROS production remains transient (2 hours) in mere wound healing. In regenerative tissue, ROS signaling triggers two distinct parallel pathways: one pathway is responsible for apoptosis, and the other pathway is responsible for JNK activation. Both events are involved in the compensatory proliferation of stump epidermal cells and are necessary for the progression of regeneration. Both events impact the Wnt, SDF1 and IGF pathways, while apoptosis only impacts progenitor marker expression. These results implicate oxidative stress in regeneration and provide new insights into the differences between healing and regeneration.
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie-CIRB, CNRS UMR 7241/INSERM U1050/Collège de France, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Gauron
authors.forename: Christine
authors.initials: C
authors.lastname: Rampon
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouzaffour
authors.forename: Eliane
authors.initials: E
authors.lastname: Ipendey
authors.forename: Jérémie
authors.initials: J
authors.lastname: Teillon
authors.forename: Michel
authors.initials: M
authors.lastname: Volovitch
authors.forename: Sophie
authors.initials: S
authors.lastname: Vriz
mesh_terms: D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D049109:Cell Proliferation; D017931:DNA Primers; D004789:Enzyme Activation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012038:Regeneration; D015027:Zebrafish
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; D048670:MAP Kinase Kinase 4